Na-dependent Regulation of Intracellular Free Magnesium Concentration in Isolated Rat Ventricular Myocytes

Changes in ionized intracellular free magnesium concentration [Mg2+]iwere measured in isolated, superfused rat ventricular myocytes using mag-fura-2. Cells were superfused with media containing high or low Mg concentrations ( [Mg]0), with and without Na (Na0) and/or Ca (Ca0). Increasing [Mg]0from 1 to 5 mmol/l in Ca-free solutions had no significant effect on [Mg2+]iwhen [Na]0was normal. However, [Mg2+]irose steadily when Na0was completely replaced by either tetramethylammonium (TMA) or K. This [Mg2+]irise was inhibited by imipramine (10μmol/l) but not by verapamil (25μmol/l). [Mg2+]ireturned rapidly from a high to its initial level on superfusing cells with basic medium containing normal Ca, Na and Mg. [Mg2+]irecovery required Na0and was inhibited by imipramine (10μmol/l). When Mg0was removed from Ca-free superfusates, the [Mg2+]idecreased whether or not Na0was present. However, [Mg2+]idecreased most when Na0was replaced by K. Neither imipramine nor verapamil affected the magnitude of this fall, but verapamil slowed it. [Mg2+]irapidly increased to normal when depleted cells were superfused with basic medium with or without Ca0. Both imipramine and verapamil slowed this recovery. Superfusion of cells with Ca-free media containing strophanthidin (20μmol/l) caused [Mg2+]ito rise, but only if the medium contained Mg (1 mmol/l). The data suggest that Mg can enter cardiac myocytes through routes which close when physiological [Mg2+]iis attained. One pathway for Mg flux is by a Na-dependent, imipramine-sensitive mechanism which is probably a Na–Mg antiport.